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J D Pearson

Publications and source records attributed to J D Pearson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Normal endothelial cell function.

Endothelial cell functions, primarily involving regulated mediator secretion or altered surface protein expression, are vital for normal homeostasis. Endothelial cells secrete the potent vasodilator and anti-platelet agent prostacyclin and nitric oxide, and also the potent vasoconstrictor peptide endothelin-1; they control the selective adhesion and emigration of leukocytes from the bloodstream; and they are the source of circulating von Willebrand factor, tissue plasminogen activator and type 1 plasminogen activator inhibitor. The properties of healthy endothelium ensure that an antithrombotic and anticoagulant balance is maintained in the bloodstream, and provide a tonic vasodilator action that controls blood flow and pressure on a minute-to-minute basis. Disturbances of normal endothelial function are strongly implicated in the pathogenesis of atherosclerosis and autoimmune vasculitic diseases including lupus.

Arteriosclerosis↗
PubMed2000

Validation of Partin tables for predicting pathological stage of clinically localized prostate cancer.

PURPOSE: The accurate prediction of pathological stage of prostate cancer using preoperative factors is a critical aspect of treatment. In 1997 Partin et al published tables predicting pathological stage using clinical stage, Gleason score and prostate specific antigen (PSA). We tested the validity of the Partin tables. MATERIALS AND METHODS: From 1990 to 1996 inclusively 5,780 patients underwent bilateral pelvic lymphadenectomy and radical prostatectomy for prostate cancer at the Mayo Clinic. However, only 2,475 of these patients met all inclusion criteria of no preoperative treatment, known biopsy Gleason score, available preoperative PSA done either before biopsy or more than 28 days after biopsy and clinical stage T1, T2 or T3a. Among the 2,475 patients 15 had positive lymph nodes and planned prostatectomy was abandoned. The receiver operating characteristics (ROC) curve area, observed and predicted Partin rates of each pathological stage, and positive and negative predictive values were used to compare the Mayo study to the Partin tables. RESULTS: The distribution of pathological stage was organ confined in 67% of Mayo cases versus 48% in the Partin study, extracapsular without seminal vesicle or node involvement in 18% versus 40%, seminal vesicle involvement without nodes in 9% versus 7% and were positive nodes in 6% versus 5%. Using the predicted probabilities of Partin et al the ROC curve area for predicted node positive disease was 0.84 for Mayo cases compared to an estimated 0. 82 in the Partin series. The ROC curve area for predicting organ confined cancer was 0.76 for the Mayo Clinic compared to an estimated 0.73 for the Partin series. The observed rates of node positive disease were similar to those predicted (Partin) based on clinical stage, PSA and Gleason score. For organ confined disease Mayo rates were consistently higher than those predicted from the Partin series using a cut point of 0.50 or greater. Positive and negative predictive values were 0.83 and 0.49 versus 0.63 and 0.70 for the Mayo Clinic and Partin series. CONCLUSIONS: Our study provides strong evidence that sensitivity and specificity of the Partin tables for external clinical sites are similar to what was reported.

Humans↗
PubMed1999

Transmembrane signalling mechanisms regulating expression of cationic amino acid transporters and inducible nitric oxide synthase in rat vascular smooth muscle cells.

The signalling mechanisms involved in the induction of nitric oxide synthase and l-arginine transport were investigated in bacterial lipopolysaccharide (LPS)- and interferon-gamma (IFN-gamma)-stimulated rat cultured aortic smooth muscle cells (RASMCs). The expression profile of transcripts for cationic amino acid transporters (CATs) and their regulation by LPS and IFN-gamma were also examined. Control RASMCs expressed mRNA for CAT-1, CAT-2A and CAT-2B. Levels of all three transcripts were significantly elevated in activated cells. Stimulated CAT mRNA expression and l-arginine transport occurred independently of protein kinase C (PKC), protein tyrosine kinase (PTK) and p44/42 mitogen-activated kinases (MAPKs), but were inhibited by the p38 MAPK inhibitor SB203580, which at 3 microM caused maximum inhibition of both responses. Induction of NO synthesis was independent of p44/42 MAPK activation and only marginally dependent on PKC, but was attenuated markedly by the PTK inhibitors genistein and herbimycin A. SB203580 differentially regulated inducible NO synthase expression and NO production, potentiating both processes at low micromolar concentrations and inhibiting at concentrations of >/=1 microM. In conclusion, our results suggest that RASMCs constitutively express transcripts for CAT-1, CAT-2A and CAT-2B, and that expression of these transcripts is significantly enhanced by LPS and IFN-gamma. Moreover, stimulation of l-arginine transport and induction of NO synthesis by LPS and IFN-gamma appear to be under critical regulation by the p38 MAPK, since both processes were significantly modified by SB203580 at concentrations so far shown to have no effect on other signalling pathways. Thus, in RASMCs, the p38 MAPK cascade represents an important signalling mechanism, regulating both enhanced l-arginine transport and induced NO synthesis.

Amino Acid Transport Systems, Basic↗
PubMed1999

Prostate-specific antigen testing of older men.

BACKGROUND: Elevated serum prostate-specific antigen (PSA) levels are predictive of a future diagnosis of prostate cancer. To test the hypothesis that older men with low PSA levels may require less intensive PSA testing because of a reduced prostate cancer detection rate, we evaluated the association between age, baseline PSA level, and prostate cancer detection. METHODS: We conducted a prospective cohort study among participants in a study of aging who had serial PSA measurements taken from age 60 or 65 years until they either were diagnosed with prostate cancer (cancer case subjects) or reached the age of 75 years (subjects without prostate cancer). The time of cancer detection among cancer case subjects was defined as the measurement date on which a PSA level above 4.0 ng/mL was detected (i.e., PSA conversion). Cancer case subjects and subjects without prostate cancer were analyzed according to baseline PSA level and age. RESULTS: All cancer case subjects in the 60-year-old cohort had baseline PSA levels above 0.5 ng/mL, and 14 of 15 cancer cases that would have been detected by a PSA conversion among the 65-year-old cohort were associated with baseline PSA levels of 1.1 ng/mL or more. If PSA testing were discontinued in men aged 65 years with PSA levels of 0.5 ng/mL or less, 100% (95% confidence interval [CI] = 78%-100%) of the cancers would still be detected by age 75 years; if PSA testing were discontinued in men aged 65 years who had PSA levels of 1.0 ng/mL or less, 94% (95% CI = 70%-100%) of the cancers would still be detected by age 75 years. CONCLUSIONS: These data suggest that a decrease in the intensity of screening among older men with low PSA values may not lead to an increase in undetected prostate cancer.

Age Factors↗
PubMed1999

Natural history of progression after PSA elevation following radical prostatectomy.

CONTEXT: In men who develop an elevated serum prostate-specific antigen level (PSA) after having undergone a radical prostatectomy, the natural history of progression to distant metastases and death due to prostate cancer is unknown. OBJECTIVE: To characterize the time course of disease progression in men with biochemical recurrence after radical prostatectomy. DESIGN: A retrospective review of a large surgical series with median (SD) follow-up of 5.3 (3.7) years (range, 0.5-15 years) between April 1982 and April 1997. SETTING: An urban academic tertiary referral institution. PATIENTS: A total of 1997 men undergoing radical prostatectomy, by a single surgeon, for clinically localized prostate cancer. None received neoadjuvant therapy, and none had received adjuvant hormonal therapy prior to documented distant metastases. MAIN OUTCOME MEASURES: After surgery, men were followed up with PSA assays and digital rectal examinations every 3 months for the first year, semiannually for the second year, and annually thereafter. A detectable serum PSA level of at least 0.2 ng/mL was evidence of biochemical recurrence. Distant metastases were diagnosed by radionuclide bone scan, chest radiograph, or other body imaging, which was performed at the time of biochemical recurrence and annually thereafter. RESULTS: The actuarial metastasis-free survival for all 1997 men was 82% (95% confidence interval, 76%-88%) at 15 years after surgery. Of the 1997 men, 315 (15%) developed biochemical PSA level elevation. Eleven of these underwent early hormone therapy after the recurrence and are not included in the study. Of the remaining 304 men, 103 (34%) developed metastatic disease within the study period. The median actuarial time to metastases was 8 years from the time of PSA level elevation. In survival analysis, time to biochemical progression (P<.001), Gleason score (P<.001), and PSA doubling time (P<.001) were predictive of the probability and time to the development of metastatic disease. An algorithm combining these parameters was constructed to stratify men into risk groups. Once men developed metastatic disease, the median actuarial time to death was 5 years. The time interval from surgery to the appearance of metastatic disease was predictive of time until death (P<.02). CONCLUSIONS: Several clinical parameters help predict the outcomes of men with PSA elevation after radical prostatectomy. These data may be useful in the design of clinical trials, the identification of men for enrollment into experimental protocols, and counseling men regarding the timing of administration of adjuvant therapies.

Disease Progression↗
PubMed1999

IgG anti-endothelial cell autoantibodies from patients with systemic lupus erythematosus or systemic vasculitis stimulate the release of two endothelial cell-derived mediators, which enhance adhesion molecule expression and leukocyte adhesion in an autocrine manner.

OBJECTIVE: To investigate the ability of anti-endothelial cell antibodies (AECA) to modulate endothelial cell function. METHODS: The effects of purified IgG from 11 patients with systemic lupus erythematosus (SLE) and 4 patients with systemic vasculitis on the expression of adhesion molecules (intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin) by human umbilical vein endothelial cells and on the adhesion of the human promyelocytic cell line U937 were examined in vitro. RESULTS: IgG from 6 of 8 AECA-positive SLE patients and 3 of 3 AECA-positive systemic vasculitis patients up-regulated adhesion molecule expression and leukocyte adhesion to endothelial cells. The 4 AECA-negative samples had no effect. Transfer experiments demonstrated that at later time points (2-8 hours) after AECA addition, endothelium-derived interleukin-1 (IL-1) accounted for the ability of AECA to increase leukocyte adhesion. However, even within very short times after addition of AECA (<30 minutes), endothelial cells released a distinct transferable mediator with similar effects. CONCLUSION: AECA in patients with SLE or systemic vasculitis may contribute to pathogenesis by increasing leukocyte adhesion to endothelial cells. AECA act by inducing the release of at least two endothelium-derived mediators, one (as-yet-unidentified) rapidly and another (IL-1) more slowly, both of which stimulate endothelial cells in an autocrine manner.

Antibodies, Blocking↗
PubMed1999

Endothelial cell function and thrombosis.

The endothelium is pivotal in the control of haemostasis and thrombosis because it is the primary source of many of the major haemostatic regulatory molecules. Healthy endothelial cells, unlike extravascular cells, are anticoagulant and antithrombotic. This is due to the regulated secretion of antiplatelet agents, including prostacyclin and nitric oxide. Following vessel injury, platelet adhesion to exposed matrix requires von Willebrand Factor, another endothelial cell product. Local generation of thrombin causes a series of receptor-mediated endothelial cell functional responses, while the surface of the endothelium is additionally the site for inactivation of thrombin by antithrombin, and its conversion to a coagulation inhibitor by interaction with thrombomodulin. Endothelial cells are also the source of circulating tissue-type plasminogen activator and its inhibitor, and Tissue Factor pathway inhibitor. In disease states, many of these endothelial cell properties are perturbed towards a more procoagulant and prothrombotic phenotype.

Animals↗
PubMed1998

Influence of finasteride on free and total serum prostate specific antigen levels in men with benign prostatic hyperplasia.

PURPOSE: Finasteride therapy for benign prostatic hyperplasia (BPH) results in a marked lowering of serum prostate specific antigen (PSA) levels. However, little is known about the effect of finasteride on unbound or free serum levels of PSA. Such information would be important since percent free PSA may substantially improve the cancer specificity of PSA testing. Thus, we prospectively studied the effect of finasteride therapy on total and free serum PSA levels. MATERIALS AND METHODS: In a randomized, placebo controlled, double-blind trial 40 men with histologically confirmed BPH (age range 52 to 78 years) were treated with either 5 mg. finasteride daily (26 patients) for 9 months or placebo (14) for 6 months. Prostate volume was assessed by transrectal ultrasound. Serum levels of free and total PSA were measured from archived serum samples stored at -70C at baseline and for as long as 9 months of treatment. RESULTS: In the finasteride group mean total PSA levels declined from 3.0 ng./ml. at baseline to 1.5 ng./ml. after 6 months of treatment (50% decrease, p <0.01). In the placebo group, with similar baseline levels, no significant change was observed. PSA density declined significantly in finasteride treated men (p <0.01) but not in men receiving placebo. The mean percent free PSA (13 to 17% at baseline) was not altered significantly by finasteride or placebo. CONCLUSIONS: Total PSA serum levels decreased by an average of 50% during finasteride therapy but percent free PSA did not change significantly. This information is potentially useful in the interpretation of PSA data used for early detection of prostate cancer in men receiving finasteride. However, further studies are required to demonstrate the use of percent free PSA to detect the development of cancer.

Aged↗
PubMed1998

The haemodynamic effects of iodinated water soluble radiographic contrast media: a review.

All classes of iodinated water-soluble radiographic contrast media (RCM) are vasoactive with the iso-osmolar dimers inducing the least changes in the vascular tone. The mechanisms responsible for RCM-induced changes in the vascular tone are not fully understood and could be multifactorial. A direct effect on the vascular smooth muscle cells causing alterations in the ion exchanges across the cell membrane is thought to be an important factor in RCM-induced vasodilatation. The release of the endogenous vasoactive mediators adenosine and endothelin may also play a crucial role in the haemodynamic effects of RCM particularly in the kidney. In addition, the effects of RCM on blood rheology can cause a reduction in the blood flow in the microcirculation. The purpose of this review is to discuss the pathophysiology of the haemodynamic effects of RCM and to offer some insight into the biology of the endothelium and vascular smooth muscle cells as well as the pharmacology of the important vasoactive mediators endothelin and adenosine.

Adenosine↗
PubMed1998

Use of multivariate models to improve prediction of pathologic stage for men with clinically localized prostate cancer.

To benefit from definitive local therapy, men with clinically localized prostate cancer should have organ-confined disease. We discuss the use of multivariate analysis using serum PSA, biopsy Gleason score and clinical stage to improve the prediction of pathologic stage. Serum PSA, biopsy Gleason scores and clinical stage correlate with pathologic stage by univariate analysis are used in this study. However, each of these variables cannot accurately predict stage for the individual patient. Several investigators have proposed clinical algorithms based on multivariate analysis to enhance pretreatment staging. For men with clinically localized prostate cancer, multivariate algorithms are useful to determine the probability of a man having organ-confined disease, seminal vesicle invasion and lymph node involvement. This information will better enable clinicians and patients to make informed decisions about appropriate treatment options.

Journal Article↗
PubMed1998

Scleroderma fibroblasts promote migration of mononuclear leucocytes across endothelial cell monolayers.

Perivascular infiltrates of inflammatory cells are a hallmark of lesional skin in scleroderma. We have explored the potential for scleroderma fibroblasts to modulate mononuclear leucocyte migration across endothelial cell monolayers in tissue culture, and to regulate expression of endothelial cell adhesion molecules. Fibroblasts were grown from skin biopsies of eight patients with active diffuse cutaneous scleroderma and from four healthy controls. Co-culture and conditioned medium transfer experiments examined the effect of soluble fibroblast products on mononuclear leucocyte (U937) cell migration across endothelial cell (1E-7) monolayers grown on tissue culture inserts. Co-culture of scleroderma, but not control fibroblasts, promoted transendothelial migration of U937 cells. Scleroderma fibroblast-conditioned medium had qualitatively similar effects and equivalent results were obtained using Jurkat-6 (T lymphocyte) cells, and with peripheral blood mononuclear cells from a patient with diffuse cutaneous scleroderma. Promotion of leucocyte migration does not appear to result from increased endothelial adhesion molecule expression, since fibroblast-conditioned medium did not up-regulate endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. Moreover, leucocyte migration across cytokine-activated endothelial cell layers in co-culture with fibroblasts was less than across resting cells, although the selective effect of scleroderma fibroblast co-culture persisted. Recombinant monocyte chemoattractant protein-1 (MCP-1) or IL-8 increased passage of mononuclear leucocytes across endothelial cell monolayers, whilst anti-MCP-1, but not anti-IL-8 antibodies, significantly reduced the effect of fibroblast conditioned medium. These data suggest that systemic sclerosis (SSc) fibroblasts promote leucocyte migration across endothelial cell monolayers in tissue culture via an MCP-1-dependent mechanism. These findings may be relevant to the perivascular mononuclear leucocyte infiltrates characteristic of early SSc lesions.

Cell Line, Transformed↗
PubMed1998

Different patterns of endothelial cell activation in renal and pulmonary vascular disease in scleroderma.

Abnormal endothelial cell function is implicated in the development of scleroderma, and in major life-threatening complications of the disease. The nature of the stimulus leading to abnormal endothelial cell function in scleroderma, scleroderma renal crisis, and scleroderma-associated pulmonary hypertension was investigated by measurement of soluble adhesion molecules, shed by activated endothelial cells, in sera from patients with these conditions. In scleroderma renal crisis, mean levels of soluble E-selectin (p < 0.05 limited scleroderma, p < 0.0001 diffuse scleroderma), sVCAM-1 (soluble vascular cell adhesion molecule-1) (p < 0.05 limited scleroderma, p < 0.05 diffuse scleroderma), and sICAM-1 (soluble intercellular adhesion molecule-1) (p < 0.0001 limited scleroderma, p < 0.0001 diffuse scleroderma) were raised, supporting a model of endothelial cell activation in this complication. Evidence for endothelial cell activation in scleroderma-associated pulmonary hypertension was inconsistent, with normal sE-selectin and normal sVCAM-1 in sera from patients with limited scleroderma and pulmonary hypertension. The endothelial cell phenotype in scleroderma-associated pulmonary hypertension may resemble that of unstimulated cells. The pulmonary vascular and renal vascular lesions associated with scleroderma may arise by distinct pathogenic mechanisms.

Acute Kidney Injury↗
PubMed1998

Activation of p42mapk in human umbilical vein endothelial cells by interleukin-1 alpha and tumor necrosis factor-alpha.

Work from this and other laboratories has identified a role for protein tyrosine kinases in interleukin-1 alpha (IL-1 alpha)- and tumor necrosis factor-alpha (TNF-alpha)-induced responses in endothelial cells. In this study, we show that activation of human umbilical vein endothelial cells (HUVEC) by IL-1 alpha leads to increased tyrosine phosphorylation of several proteins including one with a molecular mass of approximately 42 kDa. This protein was identified as p42mapk by Western blot analysis. Tyrosine phosphorylation and catalytic activation of p42mapk by IL-1 alpha was transient, reaching maximal levels after 30 min and returning to basal levels by 120-300 min. Activation of p42mapk in HUVEC was also observed in response to TNF-alpha or to the protein kinase C (PKC)-activating phorbol ester phorbol 12-myristate 13-acetate (PMA). Pretreatment of HUVEC with IL-1 alpha or TNF-alpha prevented reactivation of p42mapk by either cytokine but did not affect subsequent activation in response to PMA. Activation of p42mapk by PMA was significantly reduced by the PKC inhibitor Ro-31-8220 and completely inhibited by the protein tyrosine kinase inhibitor genistein. Genistein, but not Ro-31-8220, attenuated IL-1 alpha- and TNF-alpha-induced p42mapk activation. Taken together, the results of this study demonstrate 1) that p42mapk is transiently activated in HUVEC by IL-1 alpha and TNF-alpha, 2) that this activation is PKC independent, and 3) that a genistein-inhibitable tyrosine kinase may be an upstream regulator of cytokine-induced p42mapk activation in human endothelium.

Catalysis↗
PubMed1998

Vitamin C protects human arterial smooth muscle cells against atherogenic lipoproteins: effects of antioxidant vitamins C and E on oxidized LDL-induced adaptive increases in cystine transport and glutathione.

Glutathione (GSH) plays a key role in cellular antioxidant defenses by scavenging reactive oxygen species and reducing lipid peroxides. Intracellular GSH levels are regulated by transport of its precursor L-cystine via system xc-, which can be induced by oxidant stress. As oxidatively modified low density lipoproteins (LDLs) contribute to impaired vascular reactivity and the formation of atherosclerotic lesions, we have examined the effects of oxidized LDL and the antioxidant vitamins C and E on the L-cystine-GSH pathway in human umbilical artery smooth muscle cells (HUASMCs). Oxidized LDL, but not native LDL, elevated intracellular GSH levels and L-cystine transport via system xc- in a time-dependent (up to 24 hours) and dose-dependent (10 to 100 microg x mL-1) manner. These increases were dependent on protein synthesis and the extent of LDL oxidation, but the induction of L-cystine transport activity was independent of GSH synthesis. Pretreatment of HUASMCs for 24 hours with vitamin E (100 micromol/L) attenuated oxidized LDL-mediated increases in GSH, whereas pretreatment with vitamin C depressed basal levels and abolished oxidized LDL-induced increases in GSH and L-cystine transport in a time-dependent (3 to 24 hours) and dose-dependent (10 to 100 micromol/L) manner. Pretreatment of cells with dehydroascorbate had no effect on oxidized LDL-mediated increases in L-cystine transport and only marginally attenuated increases in GSH. Our findings provide the first evidence that vitamin C spares endogenous adaptive antioxidant responses in human vascular smooth muscle cells exposed to atherogenic oxidized LDL.

Antioxidants↗
PubMed1998

Multivariate models as predictors of pathological stage using Gleason score, clinical stage, and serum prostate-specific antigen.

The patient presented is a 58-year-old man with newly diagnosed prostate cancer who likely has at least a 10- to 15-year life expectancy. In staging this man's extent of disease, several preoperative clinical variables are provided to assess whether the patient has local disease before offering definitive surgical therapy. It has been demonstrated that the combination of several of these variables in a multivariate analysis has greater predictive power than any of these variables do alone. Multivariate analysis using clinical stage, prostate-specific antigen (PSA), and Gleason score will provide both the physician and patient with 95% confidence intervals for determining the probability of having organ-confined disease, extracapsular penetration, seminal vesicle involvement, and lymphatic metastases. Several of the clinical variables given indicate that this patient has advanced disease, such as a PSA of 12 ng/mL, a stage T2b lesion, Gleason sum 7 disease in 2 of 3 cores from the right side associated with perineural invasion, and an additional Gleason sum 7 biopsy from the contralateral apex. For a man with these preoperative variables, there is a 13% chance of organ-confined disease, an 18% probability of seminal vesicle invasion, and a 17% chance of positive pelvic lymph nodes based on a nomogram constructed from multivariate analysis. Using this information, this man should be counseled that he has a high probability (87%) of extracapsular disease and a significant risk (15% to 20%) of having either seminal vesicle or lymph node involvement. Recognizing the risks and benefits of various forms of definitive therapy for prostate cancer, the patient has additional information to make an informed decision.

Humans↗
PubMed1997

Construction of hearing percentiles in women with non-constant variance from the linear mixed-effects model.

Current age-specific reference standards for adult hearing thresholds are primarily cross-sectional in nature and vary in the degree of screening of the reference sample for noise-induced hearing loss and other hearing problems. We develop methods to construct age-specific percentiles for longitudinal data that have been modelled using the linear mixed-effects model. We apply these methods to construct percentiles of hearing level using data from a carefully screened sample of women from the Baltimore Longitudinal Study of Aging. However, the variation in the residuals and random effects from the linear mixed-effects model does not remain constant with age and frequency of the stimulus tone. In addition, the distribution of the hearing levels is not symmetric about the mean. We develop a number of methods to use the output from the linear mixed-effects model to construct percentiles that do not have constant variance. We use a transformation of the hearing levels to provide for skewness in the final percentile curves. The change in the variation of the residuals and random effects is modelled as a function of beginning age and frequency and we use this variance function to construct the hearing percentiles. We present a number of approaches. First, we use the absolute values of the population residuals to model the total deviation about the mean as a function of beginning age and frequency. Second, we model the standard deviation in the person-specific (cluster) residuals as well as the standard deviation in the estimated random effects. Finally, we use weighted least squares with the regressions on the absolute cluster residuals and absolute estimated random effects where the weights are the reciprocal of the standard deviations of their estimates.

Adolescent↗
PubMed1997

Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update.

OBJECTIVE: To combine the clinical data from 3 academic institutions that serve as centers of excellence for the surgical treatment of clinically localized prostate cancer and develop a multi-institutional model combining serum prostate-specific antigen (PSA) level, clinical stage, and Gleason score to predict pathological stage for men with clinically localized prostate cancer. DESIGN: In this update, we have combined clinical and pathological data for a group of 4133 men treated by several surgeons from 3 major academic urologic centers within the United States. Multinomial log-linear regression was performed for the simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement. Bootstrap estimates of the predicted probabilities were used to develop nomograms to predict pathological stage. Additional bootstrap analyses were then obtained to validate the performance of the nomograms. PATIENTS AND SETTINGS: A total of 4133 men who had undergone radical retropubic prostatectomy for clinically localized prostate cancer at The Johns Hopkins Hospital (n=3116), Baylor College of Medicine (n=782), and the University of Michigan School of Medicine (n=235) were enrolled into this study. None of the patients had received preoperative hormonal or radiation therapy. OUTCOME MEASURES: Simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement using updated nomograms. RESULTS: Prostate-specific antigen level, TNM clinical stage, and Gleason score contributed significantly to the prediction of pathological stage (P<.001). Bootstrap estimates of the median and 95% confidence interval of the predicted probabilities are presented in the nomograms. For most cells in the nomograms, there is a greater than 25% probability of qualifying for more than one of the pathological stages. In the validation analyses, 72.4% of the time the nomograms correctly predicted the probability of a pathological stage to within 10% (organ-confined disease, 67.3%; isolated capsular penetration, 59.6%; seminal vesicle involvement, 79.6%; pelvic lymph node involvement, 82.9%). CONCLUSIONS: The data represent a multi-institutional modeling and validation of the clinical utility of combining PSA level measurement, clinical stage, and Gleason score to predict pathological stage for a group of men with localized prostate cancer. Clinicians can use these nomograms when counseling individual patients regarding the probability of their tumor being a specific pathological stage; this will enable patients and physicians to make more informed treatment decisions based on the probability of a pathological stage, as well as risk tolerance and the values they place on various potential outcomes.

Decision Support Techniques↗